The long term objective of this research is to reduce occurrence of work-related Carpal Tunnel Syndrome (CTS). In pursuit of this goal we need to refine our understanding of the contribution of physical factors in the work environment (force, task duration, posture and repetition) to development of the disorder. Ultimately we aim to 1) characterize associations between various physical exposures (force, repetition, etc) and development of CTS due to chronic overuse;2) understand injury and recovery cycles;and 3) learn the degree to which modification of physical exposures can prevent CTS development or recurrence. We have previously developed and used a new non-human primate model to demonstrate a direct link between chronic overuse and onset of median mononeuropathy at the wrist (Dx closely associated with CTS). In this application we propose to apply this novel approach to quantifying relationships between selected work exposures and disorder development. The specific aims of this application are to: 1) To quantify the combined effects of force and wrist posture in altering the expected development of CTS;2) To quantify the recovery period associated with a natural recovery from CTS;and 3) To expand our database of maximum voluntary pinch exertion force of the macaque, which we use to predict and set experimental levels of force (as % of maximum) in our protocols. Research design and methods: Macaca fascicularis monkeys will be trained to perform a repetitive pinching task for daily food rations. Task performance data will be measured continuously: force exerted, quantity and duration of pinches, and intervals between pinches. Every two weeks Sensory Nerve Conduction Velocity (SNCV) will be assessed in the working and the non-working hand. Effects of pinch force and wrist posture will be studied using a longitudinal, between group design to characterize effect of each factor on resulting median nerve impairment, over a 18-week exposure period. Cumulative workload, degree of impairment, time to occurrence are some of the dependent measures that will be used to characterize the association between exposure factors and outcomes. MRI will be collected at baseline, at end of task exposure, and at point of recovery, to quantify change in nerve morphology. Low and higher exposure levels will allow us to explore where exposure thresholds might lay. We also propose to expand our database of macaque volitional strength, which will be a resource for future research (ours and other research teams). Relevance to public health: CTS occurs at high rates in some worker populations with a median of 28 lost work days per case, making this a disorder that is costly for employees and employers. Our previous work confirms that CTS can result from overuse of the hands. Now we need to differentiate amongst exposures, in terms of extent of nerve impairment, so that, in the long term, the risk for development or recurrence of work- related CTS can be reduced.